A.

Adsorption

- initial attachment of a virus particle to a host cell involves an interaction between specific
molecular structures on the virion surface and receptor molecules

Attachment sites on the viral surface:

• specialized attachment structures (ex. glycoprotein spikes found in viral envelopes:

rhabdoviruses)

• unique folding of the capsid proteins (ex. picornaviruses).

Host cell receptor molecules:

• receptor molecules: are specific for each virus family.

• molecular structures that usually carry out normal cell functions.

about the three-dimensional structure of virus-binding sites is being used to design antiviral drugs
that specifically interact with these sites, blocking viral adsorption

multiple copies of these molecular attachment structures are distributed around the surface of the
virion.

[Note: In some cases, the mechanism by which antibodies neutralize viral infectivity is through
antibody binding to the viral structures that are required for adsorption]

There are two principal mechanisms by which viruses enter animal cells: receptor-mediated endocytosis
and direct membrane fusion.

Failure to exit the endosome before fusion with a lysosome generally results in degradation of the virion
by lysosomal enzymes. Therefore, not all potentially infectious particles are successful in establishing
infection.

B. Penetration - the passage of the virion from the surface of the cell across the cell membrane and into
the cytoplasm

1. Receptor-mediated endocytosis: cell membrane invaginates, enclosing the virion in an

endocytotic vesicle (endosome). Release of the virion into the cytoplasm occurs by various
routes, depending on the virus, but, in general, it is facilitated by one or more viral molecules.

enveloped virus: its membrane may fuse with the membrane of the endosome, resulting in the release
of the nucleocapsid into the cytoplasm.

2. Membrane fusion: enveloped viruses (ex: human immunodeficiency virus) enter a host cell by fusion
of their envelope with the plasma membrane of the cell. Glycoproteins in the envelope of these viruses
promotes the fusion. Nucleocapsid is free in the cytoplasm, the viral membrane remains associated with
the plasma membrane of the host cell
C. Uncoating - refers to the stepwise process of disassembly of the virion that enables the expression of
the viral genes that carry out replication.

enveloped viruses: the penetration process itself is the first step in uncoating. In general, most steps of
the uncoating process occur within the cell and depend on cellular enzymes. However, in some of the
more complex viruses, newly synthesized viral proteins are required to complete the process. (The loss
of one or more structural components of the virion during uncoating predictably leads to a loss of the
ability of that particle to infect other cells, which is the basis for the eclipse period of the growth curve.
It is during this phase in the replication cycle that viral gene expression begins.

Figure 23.11 outlines the essential features of gene expression and replication of DNA viruses.

D. Mechanisms of DNA virus genome replication - Each virus family differs in significant ways from all
others in terms of the details of the macromolecular events comprising the replication cycle. The wide
range of viral genome sizes gives rise to great differences in the number of proteins for which the virus
can code.

In general, the smaller the viral genome, the more the virus must depend on the host cell to provide the
functions needed for viral replication. For example, some small DNA viruses, such as Polyomaviruses,
produce only one or two replication related gene products, which function to divert host cell processes
to those of viral replication.

Other larger DNA viruses, such as poxviruses, provide virtually all enzymatic and regulatory molecules
needed for a complete replication cycle. Most DNA viruses assemble in the nucleus, whereas most RNA
viruses develop solely in the cytoplasm.

E. Mechanisms of RNA virus genome replication - overcome two specific problems that arise from the
need to replicate the viral genome and to produce a number of viral proteins in eukaryotic host cells.
First, there is no host cell RNA polymerase that can use the viral parental RNA as a template for
synthesis of complementary RNA strands. Second, translation of eukaryotic mRNAs begins at only a
single initiation site, and they are, therefore, translated into only a single polypeptide. However, RNA
viruses, which frequently contain only a single molecule of RNA, must express the genetic information
for at least two proteins: an RNA-dependent RNA polymerase and a minimum of one type of capsid
protein.

Although the replication of each RNA virus family has unique features, the mechanisms evolved to
surmount these restrictions can be grouped into four broad patterns (or “types”) of replication

- four broad patterns (or “types”) of replication

a.) Type I—RNA viruses ssRNA) of (+) polarity that replicates via a complementary (–) strand
intermediate: as mRNA and template for complementary (–) strand synthesis

b.) Type II—viruses with a ssRNA genome of (–) polarity that replicate via a complementary (+) strand
intermediate: 1) to provide information for protein synthesis and 2) to serve as templates for
replication.
c.) Type III—viruses with a dsRNA genome:used for translation & templates for complementary (–)
strand synthesis, resulting in dsRNA progeny

d.) Type IV—viruses with a genome of ssRNA of (+) polarity that is replicated via a DNA intermediate –
the conversion of + ssRNA to dsDNA by the RNA-dependent DNA polymerase/“reverse transcriptase,”
inside the virion and integrated into the cell genome by viral “integrase” aided by the host cell RNA
polymerase

Assembly of nucleocapsids generally takes place in the host cell compartment where the viral nucleic
acid replication occurs (that is, in the cytoplasm for most RNA viruses and in the nucleus for most DNA
viruses). For DNA viruses, this requires that capsid proteins be transported from their site of synthesis
(cytoplasm) to the nucleus. The various capsid components begin to self-assemble, eventually
associating with the nucleic acid to complete the nucleocapsid.

1. Naked viruses: In naked (unenveloped) viruses, the virion is complete at this point. Release of
progeny is usually a passive event resulting from the disintegration of the dying cell and,
therefore, may be at a relatively late time after infection.

2. Enveloped viruses: In enveloped viruses, virus-specific glycoproteins are synthesized and

transported to the host cell membrane

- The response of a host cell to infection by a virus ranges from:

1) little or no detectable effect; to 2) alteration of the antigenic specificity of the cell surface due to
presence of virus glycoproteins; to 3) latent infections that, in some cases, cause cell transformation; or,
ultimately, to 4) cell death due to expression of viral genes that shut off essential host cell functions.

1. Viral infections in which no progeny virus are produced: abortive response to infection

is commonly caused by: 1) a normal virus infecting cells that are lacking in enzymes, promoters,
transcription factors, or other compounds required for complete viral replication, in which case the cells
are referred to as nonpermissive; 2) infection by a defective virus of a cell that normally supports viral
replication (that is, by a virus that itself has genetically lost the ability to replicate in that cell type); or 3)
death of the cell as a consequence of the infection, before viral replication has been completed.

2. Viral infections in which the host cell may be altered antigenically but is not killed, although
progeny virus are released: host cell is permissive, and the infection is productive (progeny virus are
released from the cell), but viral replication and release neither kills the host cell nor interferes with its
ability to multiply and carry out differentiated functions. The infection is, therefore, said to be
persistent. The antigenic specificity of the cell surface may be altered as a result of the insertion of viral
glycoproteins.

3. Viral infections that result in a latent viral state in the host cell: Some viral infections result in the
persistence of the viral genome inside a host cell with no production of progeny virus. Such latent
viruses can be reactivated months or years in the future, leading to a productive infection. Some
latently infected cells contain viral genomes that are stably integrated into a host cell chromosome. This
can cause alterations in the host cell surface; cellular metabolic functions; and, significantly, cell growth
and replication patterns. Such viruses may induce tumors in animals, in which case they are said to be
tumor viruses, and the cells they infect are transformed

4. Viral infections resulting in host cell death and production of progeny virus: Eliminating host cell
competition for synthetic enzymes and precursor molecules increases the efficiency with which virus
constituents can be synthesized. Therefore, the typical result of a productive (progeny-yielding)
infection by a cytocidal virus is the shutoff of much of the cell’s macromolecular syntheses by one or
more of the virus gene products, causing the death of the cell. Such an infection is said to be lytic. The
mechanism of the shutoff varies among the viral families.